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Advancing Disease Modeling in Animal-Based Research in Support of Precision Medicine Proceedings of a Workshop (2018) / Chapter Skim
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5 In Vitro Alternatives to Animal Models
Pages 61-68

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From page 61...
... • In vitro models allow us to find and validate genetic differences that cause disease or sensitivity. (Burridge)
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From page 62...
... The dose of doxorubicin that breast cancer patients can receive is limited by its cardiotoxicity, so eliminating or predicting toxicity would allow patients to receive a higher dose and improve the efficacy of their chemotherapy treatment, said Burridge. Researchers tested iPSCs and cardiomyocytes from patients with cardiotoxicity symptoms and their controls and discovered that the iPSCs/cardiomyocytes accurately recapitulate a patient's predilection to doxorubicin-induced cardiotoxicity.
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From page 63...
... Aiming for the gold standard answer, the research team performed a SNP correction, which reversed the doxorubicin hypersensitivity. Expanding on this information, Burridge and his colleagues are investigating whether specific RARG agonists could stimulate the RARG receptor to act as a cardio protectant for patients with doxorubicin toxicity IN VITRO CARDIAC DISEASE MODELS Megan McCain, assistant professor and the Chonette Early Career Chair in the Department of Biomedical Engineering and the Department of Stem Cell Biology and Regenerative Medicine at the University of Southern California, presented her work using in vitro models to study cardiac disease.
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From page 64...
... Traditional in vitro experiments that are conducted on two-dimensional cell cultures test cells that "from a cynical point of view could be argued to have cancer, are inbred, are diabetic, are potatoes on a stiff plastic couch without exercise, enjoy neither gender nor sex, live almost entirely in the dark, gorge themselves on sugar once a day, may be slowly suffocating in an increasingly acidic environment, live in their own excrement, never bury their dead, may take a complete or only partial
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From page 65...
... " While these experiments may end up with reproducible and statistically significant results, their relevance to human biology and disease is questionable, said Wikswo. Animal models also have genetic and physiological differences that affect their relevance to human biology as well.
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From page 66...
... Within the category of disease biology and pharmacology, MPSs could be used to discover novel mechanisms of human diseases, to identify novel compounds and clinical candidates, and to unravel the mechanism of action of drug candidates. In clinical pharmacology, MPSs can help identify problematic human haplotypes and drug–drug interactions, and to improve prediction of human exposure for compounds and clinical formulations.
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From page 67...
... Given these challenges, technologies such as iPSCs and humans-on-a-chip can serve as complementary research platforms for human-specific biology using an in vitro approach. Echoing the previous speaker, Taylor said that the human biological system is incredibly complex, with interactions and pathways between multiple organs, cells, and tissues, and many potential molecular targets for drugs.
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From page 68...
... The vLAMPS model, said Taylor, allows for cancer cell extravasation, immune cell infiltration, and delivery of factors from other organs. From his perspective, in order to fully understand liver disease and develop appropriate treatments, it is important to implement the full QSP platform, starting with patients, patient samples, and data, as well as develop multi-scaled experimental and computational models of liver diseases for drug discovery and toxicity testing.
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Key Terms

  • vitro models
  • drug discovery
  • models allow
  • human biology
  • drug response

  • computational models
  • disease models
  • drug development
  • cardiac disease
  • human cells

  • clinical trials
  • barth syndrome
  • cell cultures
  • allow researchers
  • discovery institute

  • thin films
  • biomedical engineering
  • dna damage
  • muscular thin
  • liver diseases

  • vitro cardiac
  • drug screening
  • vitro model
  • drug responses
  • conventional animal

  • drug candidates
  • human microphysiological
  • disease biology
  • potential drug
  • human haplotypes


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